Objective: The main objective of this project is to investigate whether supplementation with either vitamin E or b-carotene reduces incidence of lung and other cancers. Several hypotheses related to cancer prevention, etiology, and early detection are also being tested. Background: Abundant research indicated a role in primary cancer prevention for certain micronutrients, including vitamin E and, in particular, b-carotene, based on antioxidant and other antineoplastic properties. Methods: The ATBC Study is a randomized, placebo-controlled, double-blind, 2x2 factorial intervention trial of daily supplementation (for 5-8 years) with b-carotene (20 mg) and/or vitamin E (50 mg dl-a-tocopheryl acetate). The 29,133 participants were 50-69 year old male cigarette smokers in southwestern Finland. Serum, toenails, and questionnaire data were collected and stored at baseline, and serum, whole blood and RBC's during followup. Lung and other cancers are identified through the Finnish Cancer Registry, with central medical record and pathology reviews. Progress: Active intervention concluded in 1993, and post-trial passive followup of the cohort continues. Results of the trial showed reduced incidence in the vitamin E group for prostate (34%) and large bowel (16%) cancers. In contrast, b-carotene demonstrated no cancer preventive effects and resulted in increased cancer incidence (18% for lung cancer) and overall mortality in this study of older middle-age cigarette smokers. The possible biological interaction between b-carotene and alcohol ingestion, along with other organ-specific intervention analyses and examination of post-intervention group incidence trends are being studied. Recent etiologic analyses have shown that colon cancer risk is directly related to alcohol intake and inversely related to dietary folate, higher serum vitamin D levels are associated with reduced risk of rectal cancer, and both dietary and serum b-carotene and vitamin E levels are inversely associated with lung cancer risk. Analyses of PSA, steroid hormones, and dietary factors in relation to prostate cancer as well as several evaluations of genetic markers at different cancer sites are underway.